| Literature DB >> 29024646 |
Sizun Jiang1, Hufeng Zhou1, Jun Liang1, Catherine Gerdt2, Chong Wang1, Liangru Ke3, Stefanie C S Schmidt1, Yohei Narita1, Yijie Ma1, Shuangqi Wang4, Tyler Colson2, Benjamin Gewurz2, Guoliang Li4, Elliott Kieff5, Bo Zhao6.
Abstract
Epstein-Barr virus (EBV) transforms B cells to continuously proliferating lymphoblastoid cell lines (LCLs), which represent an experimental model for EBV-associated cancers. EBV nuclear antigens (EBNAs) and LMP1 are EBV transcriptional regulators that are essential for LCL establishment, proliferation, and survival. Starting with the 3D genome organization map of LCL, we constructed a comprehensive EBV regulome encompassing 1,992 viral/cellular genes and enhancers. Approximately 30% of genes essential for LCL growth were linked to EBV enhancers. Deleting EBNA2 sites significantly reduced their target gene expression. Additional EBV super-enhancer (ESE) targets included MCL1, IRF4, and EBF. MYC ESE looping to the transcriptional stat site of MYC was dependent on EBNAs. Deleting MYC ESEs greatly reduced MYC expression and LCL growth. EBNA3A/3C altered CDKN2A/B spatial organization to suppress senescence. EZH2 inhibition decreased the looping at the CDKN2A/B loci and reduced LCL growth. This study provides a comprehensive view of the spatial organization of chromatin during EBV-driven cellular transformation.Entities:
Keywords: CDKN2A/B; ChIA-PET; EBV regulome; EBV super-enhancers; Epstein-Barr virus; MYC
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Year: 2017 PMID： 29024646 PMCID： PMC5662195 DOI： 10.1016/j.chom.2017.09.001
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023